Recent developments in genomics and basic molecular biology have greatly increased the number of potential targets for antitumor therapy. These targets need validation before it is feasible to carry agents that act on them through the drug development process. The long-term goal of this SBIR program is to identify novel antitumor agents from natural product and synthetic chemical libraries. GA binding protein (GABP), also known as Nuclear Respiratory Factor - 2 (NRF-2), plays a crucial role in the coordination of oxidative metabolism and mitochondrial biogenesis. The objective of this application is to develop an in vitro assay to detect inhibitors of GABP function. The specific aims are: First, to develop a fluorescence-based assay for GABP function that is adaptable to a high-throughput format, and, secondly, to screen Pinnacle's natural product and compound libraries to identify entities that inhibit GABP function. In future work, these inhibitors will serve as tool compounds for testing the Central Hypothesis of this program: that compounds that act on GABP in vitro will be inhibitory to tumor cells, either alone or in combination with other agents. PROPOSED COMMERCIAL APPLICATION: This technology is intended to provide tool compounds for verification of GABP as an antitumor target.